Impairment of ovaries by 2,3,7,8-tetrachlorobenzo-p-dioxin (TCDD) exposure in utero associated with BMP15 and GDF9 in the female offspring rat

Abstract

2,3,7,8-Tetrachlorobenzo-p-dioxin (TCDD) exposure in utero had been shown to affect ovarian development and functions. However, its mechanism remained unknown. In this study, to investigate the effect of maternal exposure to TCDD on ovaries, the pregnant Sprague Dawley (SD) rats were treated with TCDD (100 ng/kg or 500 ng/kg) or only vehicle and corn oil on the day 8–14 of gestation through the gavage with a stainless-steel feeding needle (once a day). The vaginal opening and estrous cycle of female offspring rats (F1) were monitored twice a day. The ovarian histology, follicle counts, real-time PCR, western blotting and DNA methylation analysis about Gdf9 and Bmp15 were carried out in F1 rats. The results showed that exposure to TCDD (especially the dose of 500 ng/kg) in utero on GD8-14 might change the ovary weight, the concentration of E2 and FSH, the estrous cycles and the numbers of primordial and secondary follicles of the offspring rats. In addition, the mRNA and protein expression of GDF9 and BMP15 was down-regulated, while the methylation patterns of Gdf9 and Bmp15 were not affected. In conclusion, maternal exposure to TCDD could affect the ovary development and functions which were possibly associated with down-regulation of mRNA and protein expression of GDF9 and BMP15. However, the down-regulation was not related to the pattern of methylation of Gdf9 and Bmp15.